Background

According to Rome criteria, chronic constipation (CC) includes functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Some patients do not meet these criteria (No Rome Constipation, NRC). The aim of the study was is to evaluate the various clinical presentation and management of FC, IBS-C and NRC in Italy.

Methods

During a 2-month period, 52 Italian gastroenterologists recorded clinical data of FC, IBS-C and NRC patients, using Bristol scale, PAC-SYM and PAC-QoL questionnaires. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests and prescribed therapies were also recorded.

Results

Eight hundred seventy-eight consecutive CC patients (706 F) were enrolled (FC 62.5%, IBS-C 31.3%, NRC 6.2%). PAC-SYM and PAC-QoL scores were higher in IBS-C than in FC and NRC. 49.5% were at their first gastroenterological evaluation for CC. In 48.5% CC duration was longer than 10 years. A specialist consultation was requested in 31.6%, more frequently in IBS-C than in NRC. Digital rectal examination was performed in only 56.4%. Diagnostic tests were prescribed to 80.0%. Faecal calprotectin, thyroid tests, celiac serology, breath tests were more frequently suggested in IBS-C and anorectal manometry in FC. More than 90% had at least one treatment suggested on chronic constipation, most frequently dietary changes, macrogol and fibers. Antispasmodics and psychotherapy were more frequently prescribed in IBS-C, prucalopride and pelvic floor rehabilitation in FC.

Conclusions

Patients with IBS-C reported more severe symptoms and worse quality of life than FC and NRC. Digital rectal examination was often not performed but at least one diagnostic test was prescribed to most patients. Colonoscopy and blood tests were the “first line” diagnostic tools. Macrogol was the most prescribed laxative, and prucalopride and pelvic floor rehabilitation represented a “second line” approach. Diagnostic tests and prescribed therapies increased by increasing CC severity.

Chronic constipation (CC) is a common and extremely troublesome disorder that has a negative impact on social and professional life, reduces the quality of life (QoL) and represents a heavy economic burden [1–5]. CC affects about 12–17% of the world population, with a higher prevalence among females and elderly people [6–9].

A considerable amount (16 to 40%) of CC patients in different countries use laxatives, and their use is related to increasing age, symptom frequency and duration of constipation; in the USA more than $800 million are spent on laxatives each year [10, 11].

The most widely used criteria to assess CC are the Rome Criteria [12] (Table 1) which separate constipation in functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). The presence of abdominal pain relieved by defecation characterizes IBS-C. Moreover, some patients consider themselves constipated even when not showing signs or symptoms consistent with Rome criteria (here defined as “No-Rome Constipation”, NRC) [13].

Study population and questionnaires

Fifty two gastroenterologists belonging to different gastroenterological units in Italy on behalf of the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO), recorded clinical and demographic data of all patients consecutively referred for CC in a two month period (September-October 2013).

Bristol scale [14] was used to assess the stool consistency in the previous three months, while symptoms were classified according to Rome III criteria in order to verify whether the patients could be diagnosed as FC, IBS-C, or NRC. In addition, gastroenterologists were also asked to record whether the patients were clinically assessed for CC for the first time or were in follow up. Diagnostic tests, recommended specialist consultations and prescribed therapies were also recorded.

Furthermore, patients were required to fill the Patient Assessment of Constipation-Symptoms (PAC-SYM) and the Patient Assessment of Constipation-Quality of Life (PAC-QoL) questionnaires.

PAC-SYM is a 12-item self-reported questionnaire developed to assess the frequency and severity of CC symptoms. It is divided into three symptom subscales: abdominal (items 1–4), rectal (items 5–7), and stool (items 8–12) [15].

Exclusion criteria

-Patients assuming potentially constipating drugs or the onset of constipation after starting any kind of drug.

Statistical analysis

Data were analyzed by means of the SAS® System for Windows, version 9.2.

A prevalence approach was adopted and no imputation was performed for any missing data.

The association between categorical variables was analyzed using Chi-Square test or Fisher’s exact test (for cell frequencies < 5). In order to correct for multiple comparisons, pairwise tests were adjusted using the Bonferroni method.

The association between a continuous and a categorical variable (with two categories) was analyzed by the Wilcoxon-Mann–Whitney test. Finally, the association between a continuous and a categorical variable was analyzed by the Kruskal-Wallis test (or by the ANOVA in case of normal distribution). In case of pairwise comparisons, the Dunn’s test was performed. The correlation between two continuous variables was summarized by the Pearson’s correlation coefficient in case of normal data distribution, or by the Spearman’s correlation coefficient otherwise.

All statistical tests were performed with a two-sided significance level α = 0.05, therefore p-values lower than 0.05 were considered statistically significant.

The PAC-SYM and PAC-QoL total and domain scores were calculated as detailed in Additional file 1, respectively.

PAC-SYM total score and PAC-QoL total score were also analyzed through multivariate regression models, adjusting for the following independent variables: age, sex, diagnosis, duration of CC.

The duration of CC was “>1–4 years” in 23.1% (IBS-C: 33.0%; FC: 59.1%; NRC: 7.9%), “≥5years” in 21.1% (IBS-C: 27.0%; FC: 65.4%; NRC: 7.6%) and “>10 years” in 48.5% of the patients (IBS-C: 32.2%; FC: 63.9%; NRC: 4.0%). No significant difference was observed between groups but only a trend toward a shorter duration in NRC could be detected.

As shown in Table 2, 73.2% of patients reported at least one comorbidity in the previous year: depression and anxiety were more frequent in IBS-C compared to FC (p < 0.01) and NRC (p < 0.005), as well as dyspepsia (p < 0.05 vs. FC and NRC). Gastroesophageal reflux disease was more frequent in IBS-C compared to NRC (p < 0.01) and in FC compared to NRC (p < 0.05). Hypertension was found more frequently in FC than in IBS-C (p < 0.05).

The results of PAC-SYM are shown in Table 3: IBS-C mean total score was higher than FC and NRC (p < 0.0001) ones. The multivariate regression model suggested that the total score of PAC-SYM (mean: 1.6 ± 0.7) was directly related to the duration of constipation (p < 0.01), and to younger age (p < 0.0001). Abdominal symptoms subscale was significantly higher in IBS-C than in FC (p < 0.05) and in NRC (p < 0.0001). In particular, a positive association was detected between each of the first four items (discomfort, pain, bloating and stomach cramps) which constitutes the abdominal subscale and IBS-C (p < 0.0001). Fecal symptoms subscale was significantly higher in FC and IBS-C than NRC (p < 0.01). Furthermore, there was a positive correlation of the total PAC-SYM score with the number of diagnostic tests (p < 0.0005) and of suggested therapies (p < 0.05).

Table 3

PAC-SYM total score and abdominal, rectal and faecal symptoms subscales: mean values ± SD in all patients and in IBS-C, FC and NRC subgroups

In Table 4 the results of PAC-QoL are shown: IBS–C mean total score was higher than FC and NRC (p < 0.001); all the subscales, excluding the satisfaction subscale, were significantly higher in IBS-C and in FC than in NRC. Moreover, the multivariate regression model for the total score of PAC-QoL (mean: 1.8 ± 0.7) shows that this was neither related to gender, nor to age or duration of constipation. There was a statistically significant positive correlation with the number of diagnostic tests (p < 0.05), the number of suggested therapies (p < 0.0001) and the number of specialist consultations (p < 0.005).

Table 4

PAC-QoL total score and subscales (mean values ± SD) in all patients and in IBS-C, FC and NRC subgroups

1p values are referred to the differences between IBS-C, FC and NRC groups, in particular

* p < 0.001 vs IBS-C and FC; ns: not statistically significant

Digital rectal examination (DRE) was performed in 495/878 (56.4%), independently from the patients being at their first evaluation (54.7%) or at a follow up visit (56.6%). No relationship with gender was found (104 M: 61.3%; F 391: 55.2%). Patients in whom a DRE was performed were older (52.6 ± 16.6 years vs. 49.4 ± 16.7; p < 0.01), and DRE was more often performed by gastroenterologists aged over 40 years than by younger ones (60.1% vs. 44.6%; p < 0.0001).

At least a specialist consultation was requested in 277/878 (31.6%) patients, mostly psychiatric/psychological (11.5%), urological (8.1%) and gynecological (12.3% of the women) (Table 5). In IBS-C psychiatric/psychological and gynaecological consultations were more frequently requested than in NRC (p < 0.05).

Table 5

Specialist consultations requested by the gastroenterologists after their visit

1p values are referred to the differences between IBS-C, FC and NRC groups, in particular; *vs IBS-C and FC; ns: not statistically significant

Diagnostic tests were requested in 702/878 (80.0%) of the patients. Table 6 shows the different tests requested in the whole sample and in the different diagnosis subgroups (IBS-C, FC and NRC). Fecal calprotectin was more frequently prescribed in IBS-C than in FC and NRC (p < 0.0001 and p < 0.05, respectively). Thyroid function tests (p < 0.05), serology for celiac disease (p < 0.005), lactose breath test (p < 0.01) and glucose breath test (p < 0.05) were more frequently suggested in IBS-C than in FC, whereas in FC anorectal manometry was more frequently prescribed than in IBS-C (p < 0.05) and defecography more frequently than in NRC (p < 0.05). Abdominal ultrasonography was suggested in 22% of the patients without significant differences among groups.

Colonoscopy was suggested more in patients ≥50 years than in those <50 years (52.3% vs. 22.5%; p < 0.0001), more in males than in females (51.2% vs. 35.6%; p < 0.001) and more often at first evaluation than at follow-up (43.2% vs. 32.8%; p < 0.005). Also, routine blood tests (61.2% vs. 46.6%; p < 0.0001), thyroid function tests (52.0% vs. 40.2%,; p < 0.001), carcinoembryonic antigen (11.3% vs. 6.4%; p < 0.05), serology for celiac disease (19.1% vs. 13.2%; p < 0.05); and stool culture and test for ova and parasites (9.7% vs. 4.2%; p < 0.005) were requested more often at first evaluation than at follow-up. On the contrary defecography (2.5% vs. 5.6%; p < 0.05) was suggested less frequently at first visit than at follow-up. Serology for celiac disease was suggested more frequently in patients <50 years old than in patients ≥50 years old (22.0% vs. 11.3%; p < 0.0001).

Table 7 shows the suggested therapies, overall and by diagnosis. In 863/878 patients (98.3%) at least one treatment was given. Lifestyle and dietary changes were the most frequent suggestions, whereas macrogol and fiber supplements were largely the most frequently prescribed substances.

Table 7

Suggested therapies requested by the gastroenterologist after their visit

Enemas and micro-enemas/suppositories were mainly prescribed not on a daily basis but usually every other day or on demand (24.2% and 19.7%, respectively). Lifestyle changes (87.5% vs. 80.9%; p < 0.05) and dietary suggestions (91.1% vs. 83.9%; p < 0.05) were more frequently prescribed in males than in females, but anorectal surgery only in females (2.8%).

Probiotics were most frequently prescribed at first visit than at follow-up (40.9% vs. 31.5%; p < 0.01), whereas prucalopride and pelvic floor rehabilitation were more often prescribed during a follow-up visit than at first evaluation (20.1% vs. 10.6%, p < 0.0001; 23.8% vs. 15.4%, p < 0.005, respectively).

A mix of suggestions and drugs was used in many patients: in 59.5% lifestyle suggestions, changes in diet and macrogol; in 50.8% lifestyle suggestions, changes in diet and fiber supplementation; in 37.2% changes in diet, fiber supplementation and macrogol; in 37.1% lifestyle suggestions, fiber supplementation and macrogol; in 33.3% lifestyle suggestions, changes in diet and probiotics.

The present study conveys an important educational message for general practitioners, who see the majority of constipated patients, and for other specialists who could visit patients for possible comorbidities: when collecting the patient’s history, the presence of constipation should be accurately searched and treated (if possible). Waiting so many years before sending constipated patients to a gastroenterologist simply means worsening a patient’s symptoms and his/her QoL [4] and increasing the risk to develop important anatomical alterations such as perineal descent, rectocele, rectal intussusceptions, prolapse, enterocele or sigmoidocele, or increase his/her cardiovascular mortality [17].

NRC patients were usually older and often male than IBS-C, and reported fewer and less severe symptoms, softer stools and a better QoL than FC and IBS-C. On the other hand, IBS-C patients were younger and more often female, reported more severe symptoms, harder stools and a worse QoL than NRC and FC. Our results show that Rome III criteria identify patients with more severe constipation.

Recently the new Rome IV criteria have been published [18]. No substantial differences have been introduced regarding definition and classification of functional constipation: simply they state that “abdominal pain and/or bloating may be present but are not predominant symptoms (ie, the patient does not meet criteria for IBS)”. Regarding IBS the term discomfort was eliminated and the frequency of abdominal pain became at least 1 day per week instead of 3 days per month. However we think that these changes would not have a significant impact on the results of our study.

PAC-SYM and PAC-QoL questionnaires showed higher scores in IBS-C group than in FC and NRC: PAC-SYM abdominal symptom subscale, PAC-QoL mean total score, physical discomfort, psychosocial discomfort and worries and concerns subscales were found to be higher in IBS-C. This reflects the close association between the first four items of PAC-SYM (abdominal discomfort, abdominal pain, bloating, stomach cramps) and the typical symptoms of IBS. These symptoms are likely responsible for the lower QoL in IBS-C. Thus, the increase in perception of constipation severity increases impairment of the QoL, also increasing request of diagnostic tests and therapies.

Different clinical characteristics, such as type of constipation and comorbidities, may influence the clinical approach of the gastroenterologists; thus, our primary endpoint was to assess the diagnostic tools and treatment suggested by Italian gastroenterologists to their constipated patients, and the impact on the clinical subgroups.

A surprising result, deserving discussion, is that DRE was not performed in more than 40% of the patients, independently from being at first visit or at follow-up. DRE is the simplest and the most immediate method to assess anal tone and to collect information about the pelvic floor conditions and to detect early forms of rectal cancer or benign diseases [19–22]. These data should be carefully taken into account when carrying out educational campaigns on the diagnosis and treatment of CC.

The presence of comorbidities was likely the main reason for the more frequent requested consultations (psychiatric/psychological, urological, gynecological) underlining the need for a stronger collaboration among different specialists for the correct management of CC, possibly creating multidisciplinary teams.

Regarding the attitude towards diagnostic tests, we want to stress that in about four out of five patients gastroenterologists were not so confident on Rome III criteria, and prescribed at least one diagnostic test, more often in patients at first evaluation, mainly blood tests, but also colonoscopy (requested more frequently in patients older than 50 years), anorectal manometry and measurement of colonic transit time. As already shown in previous studies in a general practitioner setting, abdominal ultrasound, although not recommended by current guidelines, was quite frequently requested, especially when abdominal pain is present [23–26].

To exclude conditions potentially mimicking IBS, laboratory and breath tests were more frequently requested in these patients, whereas in FC, defecography and anorectal manometry were more frequently requested to evaluate the presence of dyssynergic defecation. In NRC patients fewer diagnostic tests were overall required, probably due to less severe symptoms and lesser impairment of the QoL.

Overall, dietetic and lifestyle suggestions were the most frequently suggested therapeutic options (>90% of the patients) (Table 7). However, in the present study, the gastroenterologists were often not confident that these could be sufficient to solve the problem and used macrogol as the first line laxative, both in association with dietetic and lifestyle suggestion and fibers.

Macrogol is effective and safe, and new liquid formulations make it easier to dose; because taste is an important factor for patients’ adherence, particularly for long-time treatment, the formulations without aroma made it more acceptable to patients [27]. On the other hand further increasing fibers intake could induce bloating and abdominal discomfort without improving colonic transit time [28]. To control the different symptoms of IBS (mainly abdominal pain and bloating) gastroenterologists also used antispasmodic drugs, psychotherapy and anti-bloating agents, whereas pelvic floor rehabilitation was suggested more often in FC patients, in whom functional defecation disorders should be more frequent.

The gastroenterologists involved in this study rarely prescribed laxatives such as lactulose/lactitole, and stimulant, emollient or saline laxatives which still represent the most used laxatives in Italy. These drugs, which cover about 40% of the Italian market [29], are more often prescribed by general practitioners [23] and other specialists than gastroenterologists.

Prucalopride, recently available on the Italian market, was prescribed in about 13% of patients although it was considered, probably because expensive, a second/third line treatment, and prescribed more frequently at a follow-up. At the time of the study, linaclotide was not yet available on the Italian market.

As previously reported for diagnostic tools, the amount of therapy prescribed also increased by increasing PAC-SYM and PAC-QoL scores; in NRC patients, who displayed lighter symptoms, fewer therapies were suggested. In conclusion, in our country a gastroenterological evaluation of CC is often delayed in patients with long lasting symptoms, colonoscopy and blood tests are considered a “first line” diagnostic tool, and DRE is insufficiently performed. Furthermore, constipation is associated with several comorbidities in most patients. Among Italian gastroenterologists macrogol is the most frequently used laxative, while in IBS-C patients a larger amount of drugs is prescribed than in FC and NRC patients.

The study also provides several educational ideas to improve the diagnostic and therapeutic approach to CC: general practitioners and other specialists should be suggested to address earlier such patients to a gastroenterologist before long-term complications occur. DRE should be performed in all patients, while echography usefulness should be resized.

Chronic constipation is a common disorder that has a remarkable impact on the quality of life. We report on diagnostic and therapeutical experiences of Italian gastroenterologists.

Patients with irritable bowel syndrome with constipation reported more severe symptoms and worsened quality of life than functional constipation. Colonoscopy and blood tests were the most prescribed tests and Macrogol was the most prescribed laxative.

This study can provide several educational ideas to improve the diagnostic and therapeutic approach to Chronic Constipation.

Acknowledgments

The authors are grateful to Dr. Elena Pasquali for her valuable help in carrying out the statistical analysis.

The members of the ChroCoDiTE StudyGroup are listed in Appendix and searchable through their individual PubMed records.

Funding

None.

Availability of data and materials

The datasets analysed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

MB, PUS, GB, participated in study concept and design, data analysis, interpretation of results, manuscript drafting and approved the final version of the manuscript. AB, RB and FG contributed to the interpretation of results, provided critical revisions to manuscript drafts and approved the final version of the manuscript. EB and PA participated in study concept and design, data collection, interpretation of results, provided critical revisions to manuscript drafts and approved the final version of the manuscript. All members of the ChroCoDiTE study group participated in data collection, provided critical revisions to manuscript drafts and approved the final version of the manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Not applicable.

Ethical approval and consent to participate

The study protocol was approved by the Ethical Committee of Pisa (study number 3841/2013 approved on March 21st, 2013) and was carried out in accordance with the Helsinki Declaration (Sixth Revision, Seoul 2008). A signed informed consent was obtained from each participant.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.